RT Journal Article SR Electronic T1 Hypoxia induces IL-18 and neutrophil influx in lung parenchyma possibly mediated by MIP-2 JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP P835 VO 40 IS Suppl 56 A1 Fadila Telarevic Cero A1 Karl Otto Larsen A1 Øystein Sandanger A1 Else Marit Løberg A1 Geir Arve Christensen A1 Ole Henning Skjønsberg YR 2012 UL http://erj.ersjournals.com/content/40/Suppl_56/P835.abstract AB Background: Increased levels of interleukin (IL)-18 have been found during experimental alveolar hypoxia and IL-18 have previously been shown to induce neutrophil migration, production of macrophage inflammatory protein 2 (MIP-2) and enhanced neutrophil functions (Verri, W.A. et al. Eur J Immunol 2007; 37:3373-80, Kinoshita, M. et al. Infect Immun. 2011; 79:2670-80).Aims: To study circulating levels of IL-18 during one week of hypoxia exposure in mice, and to investigate whether induction of IL-18 corresponds with inflammatory changes in lung parenchyma.Methods: IL-18 levels in blood was determined in C57Bl/6j mice (n=4 at each time point) exposed to hypoxic conditions at 6 hours (h) and 1-7 days. Lungs were harvested at each time point for histological analyses. Concentration of MIP-2 in blood was determined at 6h, 12h, 1-3 days.Results: The levels of circulating IL-18 were significantly increased at all time points peaking at day 1 (Figure 1A) compared to normoxic controls. Histology revealed perivascular infiltration of neutrophil granulocytes increasing from day 1 to day 3. At day 7 neutrophils were still present, but to a lesser extent than at day 3. The concentration of MIP-2 was significantly increased at day 1 (Figure 1B).Conclusions: The increase in IL-18 induced by alveolar hypoxia may promote the subsequent influx of neutrophils in lung parenchyma, possibly mediated through the neutrophil chemoattractant MIP-2.